No Prognostic, Predictive Value of Young Age for Patients With HER2-Positive Early Breast Cancer

Young age exhibited no value in the prognosis or prediction of invasive disease-free survival (IDFS) among patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer treated with pertuzumab and modern adjuvant anticancer therapies, according to an analysis of data from the APHINITY trial.

“Young age at (breast cancer) diagnosis has historically been a rationale for overtreatment,” wrote Matteo Lambertini, MD, PhD, and colleagues, adding, “Limited data with short follow-up exist on the prognostic value of age at diagnosis in HER2-positive (breast cancer) and the benefit of anti-HER2 therapy in young patients.”

The international, phase 3 APHINITY trial enrolled 4804 patients with HER2-positive breast cancer, randomized on a 1:1 basis to chemotherapy and either 1 year of pertuzumab and trastuzumab (n = 2400) or placebo and trastuzumab (n = 2405). This analysis measured age as a continuous and dichotomous variable to assess prognostic and predictive value of young age on the end point of IDFS. The patients were separated into two cohorts, those aged ≤40 years at the time of breast cancer diagnosis (n = 768), and those aged >40 years (n = 4036).

At a median follow-up of 74 (62 to 75) months, there were 86 (11.2%) patients in the young age cohort and 422 (10.5%) in the older cohort that developed an IDFS event. Young age showed no prognostic value either as a dichotomous or continuous variable (hazard ratio [HR] = 1.06, 95% confidence interval [CI] = 0.84 to 1.33 and HR = 1, 95% CI = 1 to 1.01, respectively). The lack of prognostic effect of young age was not altered by either hormone receptor status, or treatment arm. Both younger and older patients showed improved IDFS in the pertuzumab arm (HR = 0.86, 95% CI = 0.56 to 1.32 and HR = 0.75, 95% CI = 0.62 to 0.92, respectively).

“Treating young women with breast cancer is particularly complex with the risk of overtreatment based solely on age considerations,” wrote Dr Lambertini et al. “Additional preplanned analyses focused on this age group are warranted within all future studies investigating newer anticancer treatments to address potential disparities and to improve their care,” the authors concluded.

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Lambertini M, Fielding S, Loibl S, et al. Impact of age on clinical outcomes and efficacy of adjuvant dual anti-HER2 targeted therapy. J Natl Cancer Inst. 2022;114(8):1117-1126. doi:10.1093/jnci/djac096